The principal objective of this research program is to relate the genetic control of immunoglobulins to their chemical structure, biosynthesis and biological function. To achieve these objectives, we must develop monospecific antibodies to the genetic markers--i.e., the allotypic specificities--of rabbit Ig. By immunochemical analysis of family sera, genetic data will be obtained to evaluate issues of allelism and linkage. Rabbit colonies of defined genotype, homozygous or heterozygous for all known loci will continue to be developed and in particular the heavy chain haplotypes for the linked a, x, y, n, f, g, and de loci will be more completely defined. The specific aims of this proposal are as follows: to further characterize the Cu allotypes (n locus) with respect to genetic control, localization in the IgM molecule, and whether they represent structural or conformational determinants; to further analyze the complex nature of the VH allotypic subspecificities and their expression among Ig populations of different classes; to characterize the common idiotype of selected anti-allotype Abs (eg. anti-a2 Ab) by means of anti-idiotype antisera and clonotype analysis using isoelectric focusing; to characterize the idiotype specificities that arise as a result of allotype suppression and are unique to a single rabbit and which may reflect a restricted repetoire of VH genes; to develop allotype suppressed rabbits by a combination of allo-Ab followed by autoimmunization; to develop auto-Ab to the suppressed allotype thereby maintaining the suppression by a self regulating mechanism and greatly facilitating the development of allotype suppressed rabbit colonies for studies on the minor Ig populations (x, y, and c loci) and on regulatory mechanisms which maintain the suppression; to determine the effect of allotype suppression by Ab to one allotypic specificity of the heavy chain chromosomal region on other allotypic specificities of the same haplotype or the alternative haplotype; to investigate the mechanism of allotype suppression in vitro and in vivo; to investigate the question of allelic exclusion.